Value In Gastric Cancer Research Articles

NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.

Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear. To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results. The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy. Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.

Diagnostic efficacy of SEPT9 and PAX5 gene methylation in gastrointestinal cancer and precancerous lesions.

To assess the diagnostic efficacy of SEPT9 along with PAX5 gene methylation detection in gastrointestinal cancer and precancerous lesions, the peripheral blood of 62 patients with gastric cancer (GC) and 60 patients with no evidence of disease (as the control group) were retrospectively collected. The methylation rates of PAX5 and SEPT9 gene promoters in blood samples of GC group were detected by PCR. At the same time, the differences in methylation rates of genes in the two groups were compared, and the predictive value of plasma methylation PAX5 and SEPT9 in GC was evaluated by receiver operating characteristic (ROC) curve. We found that there were 41 cases of methylated PAX5 gene promoter region and 39 cases of methylated SEPT9 gene promoter region in GC group. The control group contained 14 cases of PAX5 gene promoter methylation and 12 cases of RNF¹80 gene promoter methylation. The occurrence of PAX5 promoter methylation was correlated with age of GC patients. There were statistically significant differences in mSEPT9 gene in patients with different TNM stages. Kaplan-Meier survival curve analysis revealed that the three-year overall survival rate of GC patients with PAX5 methylation was lower than that of GC patients without PAX5 methylation. No significant difference was discovered in 3-year overall survival rate between GC patients with SEPT9 methylation and those without SEPT9 methylation. Combined detection could not improve the diagnostic value of GC, but could promote diagnosis sensitivity. In summary, the risk of PAX5 and SEPT9 gene methylation in GC patients presents higher when compared with healthy people. PAX5 gene methylation is closely related to age, while SEPT9 is closely related to tumor TNM stage, and PAX5 gene methylation can decrease the survival rate of GC patients. Detection of PAX5 gene methylation level can assist in evaluating the prognosis of GC patients.

Cuproptosis-related gene DLAT is a biomarker of the prognosis and immune microenvironment of gastric cancer and affects the invasion and migration of cells.

Cuproptosis is a novel cell death dependent on mitochondrial respiration and regulated by copper. This study aimed to investigate the cuproptosis-related gene DLAT potential value in gastric cancer (GC). Bioinformatics was used to analyze DLAT expression. DLAT expression in GC cell lines was detected using qRT-PCR. Cell proliferation ability was assessed using CCK8 and cell cycle assay. Cell migration and invasion were assessed using wound healing and transwell assay. A prognostic assessment was performed through survival and Cox regression analysis. DLAT protein expression was analyzed through HPA immunohistochemistry. Biological functions and processes were analyzed through GO and KEGG enrichment analysis and PPI. Correlation with immune cell infiltration and immune checkpoint genes was analyzed for DLAT. DLAT expression was upregulated in GC tissues and cells and correlated with shorter survival for patients. Age, gender, histological typing, lymph node metastasis, and distant metastasis were identified as independent prognostic factors affecting OS in GC. DLAT protein was upregulated in GC. The biological functions and pathways enriched in DLAT were mainly linked to mitochondrial respiration and the TCA cycle. The expression of DLAT was found to be positively correlated with the infiltration of Th and Th2 immune cells and only positively correlated with the expression of the BTN2A1 immune checkpoint gene. DLAT has the potential to serve as a prognostic assessment factor in GC. The expression of DLAT was correlated with immune infiltration and tumor immune escape, providing a new target for immunotherapy of GC.

Multi-omics analysis of the prognostic and biological role of cuproptosis-related gene in gastric cancer.

A considerable number of gastric cancer (GC) patients cannot receive benefits from current treatments. We aimed to identify possible biomarkers of cuproptosis-related genes (CRGs) in GC patients, which may help guide precision medicine-based decision-making. RNA sequencing data, copy number variations (CNVs) data, and single nucleotide variant (SNV) data were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Cancer Analysis (GSCA) database. Chi-squared test was adopted to screen differentially expressed CRGs (DE-CRGs) between samples from 14 kinds of carcinoma and adjacent tissue samples. Then, GC samples were divided into high- and low-expressed groups based on DE-CRGs for further survival analyses and the selection of biomarkers. Methylation sites related with biomarkers were acquired. The correlation between immune cells and biomarkers was verified. Finally, miRNA-mRNA, TFs-mRNA, and co-expression networks were established to detect factors with regulating effects on biomarkers. Three CRGs including LIAS, GLS, and CDKN2A were identified as biomarkers in GC patients. Three methylation sites with a significant survival effect including cg13601799, 07562918, and 07253264 were acquired. Then, we found that B cells native was significantly correlated with CDKN2A, four immune cells such as T cells regulatory are significantly correlated with GLS, and two immune cells such as T cells CD4 memory activated were significantly correlated with LIAS. Moreover, 10 miRNAs in the miRNA-mRNA network and three transcription factors (TFs) in the TFs-mRNA network had a significant correlation with overall survival (OS). Finally, 20 enrichment functions were obtained on the basis of the co-expression network. Three biomarkers with a prognosis prediction value of GC were found, and multi-factor regulatory networks were constructed to screen out 13 factors with regulating influences of biomarkers.

APOA1 mRNA and serum APOA1 protein as diagnostic and prognostic biomarkers in gastric cancer.

Gastric cancer (GC) remains a formidable challenge in oncology, ranking as a leading cause of cancer mortality globally. This underscores an urgent need for innovative prognostic markers that can revolutionize patient management and outcomes. Recent insights into cancer biology have spotlighted the profound influence of lipid metabolism alterations on tumorigenesis, tumor progression, and the tumor microenvironment. These alterations not only fuel cancer cell growth and proliferation but also play a strategic role in evading immune surveillance and promoting metastasis. The intricate web of lipid metabolism in cancer cells, characterized by deregulated uptake, synthesis, and oxidation of fatty acids (FAs), opens new avenues for targeted therapeutic interventions and prognostic evaluations. Specifically, this study zeroes in on apolipoprotein A-I (APOA1), a key player in lipid metabolism, to unearth its prognostic value in GC. By delving into the role of lipid metabolism-related genes, particularly APOA1, we aim to unveil their potential as groundbreaking biomarkers for GC prognosis. This endeavor not only aims to enhance our understanding of the molecular underpinnings of GC but also to spearhead the development of lipid metabolism-based strategies for improved diagnostic, prognostic, and therapeutic outcomes. Transcriptomic and clinical data from GC patients and healthy individuals were sourced from The Cancer Genome Atlas (TCGA) database, a comprehensive project that molecularly characterizes over 20,000 primary cancer and matched normal samples across 33 cancer types. Significantly differentially expressed lipid metabolism-related genes were identified using the "limma" package in R. Prognostic genes were selected via univariate Cox regression analysis. Differential gene enrichment analysis was performed using Metascape (http://www.metascape.org). The Human Protein Atlas (HPA, https://www.proteinatlas.org) provided information on APOA1 protein expression in GC and healthy tissues. Immune cell infiltration was analyzed using the CIBERSORT algorithm (http://cibersort.stanford.edu). Significant differences in lipid metabolism-related gene expression were observed between GC and normal tissues, closely linked to FA metabolism, oxidoreductase activity, and sphingolipid metabolism. APOA1 emerged as a potential prognostic biomarker by intersecting prognostic and differentially expressed lipid metabolism genes. Immunohistochemical analysis confirmed APOA1 downregulation in GC. The receiver operating characteristic (ROC) analysis demonstrated its predictive value, with the area under the curve (AUC) being 0.64 [95% confidence interval (CI): 0.52-0.76]. APOA1 expression correlated with immune cell infiltrations. Clinical serum APOA1 results revealed lower levels in GC patients (1.38 vs. 1.26; P<0.05), associated with poor prognosis (hazard ratio =1.50; P<0.001) and clinical characteristics. ROC analysis of serum APOA1 demonstrated good diagnostic ability (AUC: 0.63, 95% CI: 0.61-0.65). Serum APOA1 levels significantly increased after treatment. This study highlights lipid metabolism reprogramming in GC and identifies APOA1 as a potential diagnostic and prognostic biomarker, suggesting its clinical utility in managing GC.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. As a newly discovered type of non-coding RNAs, transfer RNA (tRNA)‍-derived small RNAs (tsRNAs) play a dual biological role in cancer. Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC. In this work, we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation, migration, and invasion of GC cells in vitro. The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3' untranslated region (UTR) site of acyl-coenzyme A dehydrogenase short/branched chain (ACADSB). In addition, ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells. Next, we used Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis. Finally, we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level, as well as the changes in reactive oxygen species (ROS) levels by flow cytometry. In summary, this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB, thereby promoting GC progression. It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis

AimsTo investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. ResultsTranscriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. ConclusionCPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis

To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC. GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR. Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC, TIMP1, THBS2, COL6A3 and THY1 were significantly up- regulated and TFF1, GKN1, TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC, TIMP1, THBS2, COL6A3, TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC, THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC, TIMP1, THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses. SPARC, TIMP1, THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Exosomal miRNAs from neutrophils act as accurate biomarkers for gastric cancer diagnosis

BackgroundGastric cancer (GC) is the third leading cause of cancer-related death worldwide. Sensitive and accurate biomarkers can greatly aid in early diagnosis and favorable prognosis. Neutrophils are the most abundant immune cells in human circulation and play a critical role in tumor progression. Neutrophil-derived exosomes (Neu-Exo) contain abundant bioactive molecules and are critically involved in disease progression. MethodsWe proposed a Dynabeads-based (CD66b antibody-coupled) separation and detection system for Neu-Exo analysis. Dual antibody-assisted fluorescent Dynabeads was established to detect Neu-Exo abundance. MiRNA signature of Neu-Exo was identified by RNA sequencing. QRT-PCR and droplet digital PCR (ddPCR) were used for candidate miRNA detection and the potential of Neu-Exo miRNAs in the diagnosis of gastric cancer was evaluated. ResultsDual antibody-assisted fluorescent Dynabeads obtained a detection limit of 7.8 × 105 particles/mL of Neu-Exo and a recovery rate of 81 % under optimized conditions. ROC curve indicated that the abundance of CD66b+ Neu-Exo could well distinguish GC patients from healthy controls (HC) (AUC > 0.8). Additionally, miR-223-3p was found among the top differentially expressed miRNAs in Neu-Exo and presented superior diagnostic value in gastric cancer. Droplet digital PCR (ddPCR) significantly improved the diagnostic efficiency to differentiate GC patients from HC and benign gastric diseases (BGD) patients (AUC > 0.9). ConclusionThe Dynabeads-based separation and detection system, assisted with ddPCR analysis, provides a promising platform to enrich Neu-Exo and analyze miRNA profile for gastric cancer liquid biopsy.

Pan-Cancer Analysis of ART1 and its Potential Value in Gastric Cancer.

Objective: To comprehensively explore the impact of Mono-ADP-ribosyltransferases-1 expression on both prognosis and the intricate landscape of the tumor immune microenvironment across diverse cancer types, our study seeks to delve into the multifaceted interplay between Mono-ADP-ribosyltransferases-1 expression levels and their implications for clinical outcomes and the dynamic milieu of immune responses within tumors. Methods: Genomic, transcriptomic, and clinical datasets spanning diverse cancer types were meticulously curated from The Cancer Genome Atlas and Genotypic Tissue Expression repositories. Initially, our inquiry focused on discerning the prognostic significance and immunological implications of Mono-ADP-ribosyltransferases-1 expression across this heterogeneous spectrum of malignancies. Subsequently, we scrutinized the relationships between Mono-ADP-ribosyltransferases-1 expression levels and a spectrum of factors including RNA modification genes, genetic mutations, and the emergent concept of tumor stemness. Employing functional enrichment analyses, we endeavored to unravel the underlying mechanistic pathways modulated by Mono-ADP-ribosyltransferases-1. Leveraging Bayesian co-localization analysis, we sought to discern the spatial convergence of Mono-ADP-ribosyltransferases-1 expression particularly within the context of digestive tract tumors. Lastly, to corroborate our findings, we conducted in vitro experiments, specifically focusing on Gastric Cancer, thus corroborating the putative oncogenic role attributed to Mono-ADP-ribosyltransferases-1 in this malignancy. Results: Across diverse tumor types, Mono-ADP-ribosyltransferases-1 expression exhibits distinctive patterns compared to normal and adjacent tissues, thereby intertwining with the prognostic outcomes of numerous cancer patients. Noteworthy findings from our immune role identification underscore the pivotal involvement of Mono-ADP-ribosyltransferases-1 in the landscape of tumor immunotherapy. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis elucidates the enrichment of Mono-ADP-ribosyltransferases-1-associated genes predominantly within the NF-kB, Foxo, and PI3K-Akt signaling cascades, shedding light on potential mechanistic pathways underlying its influence. Bayesian co-localization analysis unveils a compelling genetic correlation between Mono-ADP-ribosyltransferases-1 and digestive tract tumors, accentuating its relevance within this specific oncological domain. Importantly, experimental validation attests to the therapeutic promise of targeting Mono-ADP-ribosyltransferases-1 in the treatment paradigm of gastric cancer, thereby underscoring its potential as a viable therapeutic target deserving of further exploration and clinical translation. Conclusion: This comprehensive pan-cancer analysis unveils crucial insights into the intricate role played by Mono-ADP-ribosyltransferases-1 in the tumorigenesis of diverse malignancies, thereby establishing a robust theoretical framework for subsequent in-depth investigations. Leveraging these insights, targeting Mono-ADP-ribosyltransferases-1-related signaling pathways within the dynamic tumor microenvironment emerges as a promising avenue for novel therapeutic interventions in the realm of tumor immunotherapy. By delineating the interplay between Mono-ADP-ribosyltransferases-1 expression and tumorigenic processes across various cancer types, this study paves the way for innovative therapeutic strategies aimed at disrupting oncogenic signaling cascades and bolstering immune-mediated antitumor responses.

RELAÇÃO DE LINFONODOS METASTÁTICOS VS. LINFONODOS RESSECADOS (N-RATIO) TEM IMPLICAÇÕES PROGNÓSTICAS NO CÂNCER GÁSTRICO

ABSTRACT BACKGROUND: Lymph node status is vital for gastric cancer (GC) prognosis, but the conventional pN stage may be limited by variations in lymphadenectomy and stage migration. The N-Ratio, which assesses the ratio of metastatic to resected lymph nodes, emerges as a promising prognostic tool. AIMS: To assess N-Ratios prognostic value in GC, particularly in patients with &lt;25 resected lymph nodes. METHODS: Patients who underwent gastrectomy with curative intent for GC were retrospectively evaluated. The N-Ratio categories were determined using the ROC curve method, and the area under the curve (AUC) was used as a measure of performance in predicting recurrence/death. RESULTS: A total of 561 GC patients were included in the study, 57% had pN+ status, and 17.5% had &lt;25 resected lymph nodes. N-Ratio, with a mean of 0.12, predicted survival with 74% accuracy (AUC=0.74; 95%CI 0.70–0.78, p&lt;0.001). N-Ratio categories included: N-Ratio 0 (43%); N-Ratio 1 (12.3%); N-Ratio 2 (31.6%); and N-Ratio 3 (13.2%). Disease-free survival (DFS) varied among all N-Ratio groups, with N-Ratio 3 showing worse survival than pN3 cases (DFS=21.8 vs. 11 months, p=0.022, p&lt;0.05). In cases with &lt;25 resected lymph nodes, DFS was not significantly worse in N-Ratio 0 (68.8 vs. 81.9%, p=0.061, p&gt;0.05) and N-Ratio 1 (66.2 vs. 50%, p=0.504, p&gt;0.05) groups. The DFS of N-Ratio-0 cases with &lt;25 lymph nodes was similar to N-Ratio 1 cases. CONCLUSIONS: N-Ratio influenced survival in GC patients, especially in advanced lymph node disease (N-Ratio 3). Considering that N-Ratio does not impact pN0 cases, individualized prognosis assessment is essential for patients with &lt;25 resected lymph nodes.

Clinical utility of multi-row spiral CT in diagnosing hepatic nodular lesions, gastric cancer, and Crohn's disease: a comprehensive meta-analysis.

A retrieval of relevant literature on hepatic nodular lesions, gastric cancer (GC), and Crohn's disease (CD) was conducted from Chinese and English databases. Meta-analysis was performed using Review Manager 5.4 software and the MIDAS package in Stata 18.0. Results from 11 studies comprising 1847 patients were synthesized. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with 95% confidence intervals were: 0.91 (0.84-0.95), 0.73 (0.65-0.79), 3.30 (2.60-4.30), 0.13 (0.07-0.23), and 26.00 (12.00-53.00), respectively. Significant statistical heterogeneity was found in sensitivity and specificity (P<0.05), with specificity heterogeneity originating from n, type, and mode (P<0.05). Sensitivity and specificity for n, type, object, and mode were non-heterogeneous (P>0.05). The combined AUC from SROC curve analysis of the 11 studies was 0.85. Deeks' funnel plot asymmetry test yielded a p-value of 0.01, indicating potential bias across studies in the diagnostic odds ratio funnel plot. Fagan's nomogram demonstrated that using CT for diagnostic modeling increased the post-test probability of correctly diagnosing hepatic nodular lesions, GC, and CD from 50.00% to 77.00%. Overall, multi-detector CT shows good diagnostic value for hepatic nodular lesions, GC, and CD, supporting its clinical flexibility based on patient-specific considerations.

Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer.

Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II-III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28-5.14, p = 0.008). The Kaplan-Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10-0.93, p = 0.042). LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.

The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer.

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

Integrated analysis of single-cell and bulk RNA-sequencing data reveals the prognostic value and molecular function of THSD7A in gastric cancer.

The biological role and prognostic value of thrombospondin domain-containing 7A (THSD7A) in gastric cancer remain unclear. Our purpose was to determine the molecular mechanisms underlying the functioning of THSD7A and its prognostic value in gastric cancer. Gastric cancer-associated single cell and bulk RNA sequencing data obtained from two databases, were analyzed. We used bulk RNA sequencing to examine the differential expression of THSD7A in gastric cancer and normal gastric tissues and explored the relationship between THSD7A expression and clinicopathological characteristics. Kaplan-Meier survival and Cox analyses revealed the prognostic value of THSD7A. Gene set enrichment and immune infiltration analyses were used to determine the cancer-promoting mechanisms of THSD7A and its effect on the immune microenvironment. We explored the relationship between THSD7A expression and sensitivity of anti-tumor drugs and immune checkpoint levels. Biological functions of THSD7A were validated at single-cell and in vitro levels. THSD7A expression was significantly increased in gastric cancer samples. High THSD7A expression was associated with poor clinical phenotypes and prognoses. Cox analysis showed that THSD7A was an independent risk factor for patients with gastric cancer. Enrichment analysis suggested that epithelial-mesenchymal transition and inflammatory responses may be potential pro-cancer mechanisms of THSD7A. Upregulation of THSD7A promoted infiltration by M2 macrophages and regulatory T cells. High THSD7A expression suppressed the sensitivity of patients with gastric cancer to drugs, such as 5-fluorouracil, bleomycin, and cisplatin, and upregulated immune checkpoints, such as HAVCR2, PDCD1LG2, TIGIT, and CTLA4. At the single cell level, THSD7A was an endothelial cell-associated gene and endothelial cells overexpressing THSD7A showed unique pro-oncogenic effects. In vitro experiments confirmed that THSD7A was overexpressed in gastric cancer samples and cells, and that knocking out THSD7A significantly inhibited gastric cancer cell proliferation and invasion. THSD7A overexpression may be a unique prognostic marker and therapeutic target in gastric cancer. Therefore, our study provides a new perspective on the precise treatment of gastric cancer.

Cytoplasmic CCR7 (CCR7c) Immunoexpression Is Associated with Tumor Invasion in Gastric Cancer

Background: This study investigates the CCR7 chemokine receptor’s prognostic value in gastric cancer and its relationship to metastasis.&#x0D; Materials and Methods: Normal and adjacent tumor cells in 70 patients with gastric cancer were evaluated for CCR7 expression using immunohistochemical staining. The prognostic values of high and low levels of expression of CCR7 were also evaluated by multivariate and univariate analyses.&#x0D; Results: Analysis indicated high expression of CCR7 in 52.9% of tumor tissue. Moreover, high expression of CCR7 was significantly related to metastasis of lymph nodes (p = 0.00). In addition, high expression of CCR7 had a positive correlation to the disease stage (p = 0.00), age of ≥50 years (p = 0.019), male gender (p = 0.024), vascular involvement (p = 0.009), histology of tumor adenocarcinoma (p = 0.00), and poor tumor differentiation (p = 0.00). However, the high expression of the CCR7 marker was not related to the tumor size.&#x0D; Conclusion: Based on our results, CCR7 expression in gastric cancer can be considered a clinical prognostic indicator in patients with gastric cancer.

The Memorial Sloan Kettering Prognostic Score: Correlation with survival in patients with advanced gastric cancer.

Notwithstanding that the past decade has witnessed unprecedented medical progress, gastric cancer (GC) remains a leading cause of cancer death, highlighting the need for effective prognostic markers. The Memorial Sloan Kettering Prognostic Score (MPS) has been validated as a valuable prognostic tool for patients with metastatic pancreatic adenocarcinoma (mPDAC). This study aimed to assess the prognostic value of the MPS in advanced GC. Data from 367 patients were analyzed in the present study. The MPS for each patient was calculated based on the sum of scores based on the neutrophil-to-lymphocyte ratio and serum albumin levels. Multivariate analyses were performed to identify the independent clinicopathological parameters associated with overall survival (OS). Further subgroup analyses based on clinicopathological features were conducted. Patients with MPS 0 (n = 161), MPS 1 (n = 158), and MPS 2 (n = 48) exhibited significantly different OS, with a median survival duration of 20.7 (95%CI: 12.2-29.2), 14.9 (95%CI: 12.5-17.3), and 12.7 (95%CI: 9.3-16.0) months, respectively (p < 0.001). Significant differences in survival were observed among different groups of patients receiving chemotherapy (18.5 months vs. 14.7 months vs. 11.0 months, p = 0.03) or the subgroup receiving chemotherapy plus immunotherapy as first-line treatment (32.6 months vs. 17.7 months vs. 12.7 months, p = 0.02). The MPS was identified as an independent prognostic factor in multivariate analysis. During subgroup analyses, MPS-low (MPS 0) was consistently associated with a better prognosis than MPS-high (MPS 1 or 2). MPS is a practical, simple, and useful prognostic tool for patients with advanced GC. Further studies are warranted to validate its prognostic value in advanced GC.

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS.

Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated. To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression. Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis. The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC. This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Diagnostic biomarker KIF23 is associated with immune infiltration and immunotherapy response in gastric cancer.

Kinesin family member 23 (KIF23), an index of tumor proliferation, can serve as a prognostic marker in numerous tumors. However, the relationship between KIF23 expression and diagnostic value, immune infiltration, and immunotherapy response remains unclear in gastric cancer(GC). We primarily demonstrated that GC tissue had higher levels of KIF23 expression than the adjacent normal tissue on mRNA and protein levels. The ROC analysis revealed KIF23 had an outstanding diagnostic value of GC in the training and validation set (AUC = 0.958, and AUC = 0.86793, respectively). We discovered that KIF23 was positively associated with age, histological type, and H. pylori infection of GC. Subsequently, the KIF23 expression level was correlated with the gene mutation, function enrichment, immune cell infiltration, and immune cell marker of GC based on multiple online websites and R software. KIF23 expression was related to the infiltration of CD8+ T cells, CD4+T cells, macrophages, and dendritic cells in GC. Especially, KIF23 expression was positively significantly associated with the Th1 cell marker STAT1 (Signal transducer and activator of transcription 1). Patients with high KIF23 expression exhibited greater immune cell infiltrates, including T cell CD4+ memory helper, Treg, and M1 cells, which indicated that high KIF23 expression is more conducive to immunosuppression. Finally, KIF23 expression had a positive relationship with TMB and MSI, and affected the immune microenvironment in GC tissues by increased expression of ICPs such as CD274(PD-L1), CTLA4, HAVCR2, and LAG3. Our study uncovered that KIF23 can serve as an immune-related biomarker for diagnosis and immunotherapy response of GC.